Secondary caries and restoration fracture are the most frequent reasons for replacement of existing tooth restorations. Replacement dentistry accounts for 70% of all operative work and costs $5 billion/year in the US. In preliminary studies, nanoparticles of calcium phosphates (Ca-PO4) and calcium fluoride (CaF2) were synthesized for the first time and incorporated into dental resins. The objectives of the proposed research are to: (1) develop a new generation of stress-bearing, caries-inhibiting nancomposites;(2) determine the effects of nanoparticle sizes and compositions, and esthetic glass co-filler reinforcement;(3) design nanocomposites with tooth caries-inhibition capability exceeding current releasing restoratives, and long-term mechanical durability and wear that match current stress-bearing, non-releasing composite;and (4) establish nanocomposite processing methods and structure-performance relationships. AIM 1 will test the hypotheses that: (i) Decreasing the nanoparticle size will significantly increase the release to be much higher than a control composite containing traditional Ca-PO4 particles;(ii) Glass reinforcement will improve the nanocomposite strength, toughness and wear to match commercial stress-bearing, non-releasing composite, and to be 2-3 fold better than current releasing restoratives. AIM 2 will test the hypotheses that: (i) Fluoride release from nanocomposite is inversely proportional to CaF2 nanoparticle size, and is proportional to CaF2 volume fraction;(ii) Nanocomposites will have strength and toughness 2-3 fold greater than a resin-modified glass ionomer control, and wear depth 1/3 that of the control. AIM 3 will test the hypotheses that: (i) Tooth caries inhibition depends on nanoparticle size and composition;(ii) Nanocomposites, with much higher mechanical properties, can prevent tooth caries much more effectively than current releasing restoratives. AIM 4 will test the hypotheses that: (i) Mechanical response to water-aging and thermal-cycling will depend on nanoparticle size and composition;(ii) Nanocomposites, with Ca, PO4 and F release exceeding current releasing restoratives, will possess mechanical properties that match commercial stress-bearing, non-releasing composite, after 2 years of water-aging and thermal cycling;(iii) After water-aging/thermal cycling, nanocomposites will exceed the long-term ion release of the controls. The expected outcomes are: (1) A new generation of stress-bearing nanocomposites with release of high levels of cavity-fighting agents to inhibit tooth caries;(2) Significant impact on dentistry by overcoming the two major problems: secondary caries, and restoration failure;(3) Novel nanocomposite processing methods, structure-property relationships and models, that can be applied to dental and bone tissue engineering where stress-bearing and controlled-release capabilities are both important. PROJECT NARRATIVE: This project, utilizing novel nanoparticles synthesized in our laboratory for the first time, seeks to develop a new generation of stress-bearing, tooth caries-inhibiting nancomposites to overcome secondary caries, which is the major reason for replacement of existing restorations. Replacement dentistry accounts for 70% of all operative work and costs $5 billion/year in the US alone. Furthermore, this project will establish novel nanocomposite processing methods, structure-property relationships and models, which can benefit dental and bone tissue engineering where load-bearing and controlled-release capabilities are both important.